Natural killing (NK) is described as the cytotoxic activity of lymphoid cells occurring in the absence of any apparent stimulation against certain target cells. In the human, the activity seems to reside in a minor mononuclear lymphoid cell population having receptors for the Fc portion of Ig, lacking detectable SIg and phagocytic activity. The specificity of NK is unclear though the killing is selective. The object of the work proposed here is to investigate the exact nature and possibly heterogeneity of the effector cells involved in NK, and their specificity. Characterization of NK cells will be performed with NK cell enriched population obtained by the application of specific cellular and subcellular immunoadsorbent. We will search for cell markers characteristic of NK cells by using sera from sensitized individuals (multiparous women and hypertransfused patients). The possible relationship of NK to antibody dependent cellular cytotoxicity (ADCC) will be explored by using normal cells and cells from X-linked agammaglobulinemia patients that lack ADCC but have NK activity. In light of the possibility that NK has in vivo relevance to tumor resistance we will evaluate the level of NK in material obtained from ovarian cancer patients. NK activity of patients will be compared to controls by testing the effector cells against autochthonous and allogeneic tumor targets. Genetic factors associated with NK will be studied using families with known genetic background. The overall aim is to clarify the nature and specificity of the effector cells and their possible role in ovarian cancer.